Severe Acute Respiratory Syndrome (SARS) is an emerging new infectious disease caused by a novel coronavirus that infects humans. See Ksiazek et al., New Engl. J. Med. (http://content.nejm.org/cgi/reprint/NEJMoa030781 v2.pdf, published Apr. 10, 2003). SARS is fatal in about 4–10% of cases reported so far. Initially described in mid February, 2003 in China's Guangdong province as atypical pneumonia, by mid-March, 2003 the World Health Organization (WHO) had received reports of more than 150 new suspected cases of unknown origin or cause. By mid April, 2003, over 4400 cases with 263 deaths of patients diagnosed with symptoms of SARS have been documented from 26 different countries, including Canada, China, Hong Kong, Indonesia, Philippines, Singapore, Thailand, Viet Nam and the United States. In light of the rapid spread of SARS to several countries in a short period of time, the World Health Organization issued a global alert and provided emergency guidance for travellers and airlines. In only a few months after the outbreak was first recognized, SARS became a worldwide threat to global health and global economies. There are presently no known therapies that are effective against SARS, and no vaccine is available. Accordingly, there is an urgent need for antiviral agents that can control or prevent SARS in infected individuals, and that can prevent SARS from spreading.
In general, SARS begins with a fever greater than 100.4° F. [>38.0° C.]. Other symptoms may include headache, an overall feeling of discomfort, and body aches. Some people also experience mild respiratory symptoms. After 2 to 7 days, SARS patients may develop a dry cough and have trouble breathing.
The primary way that SARS appears to spread is by close person-to-person contact. Most cases of SARS have involved people who cared for or lived with someone with SARS, or had direct contact with infectious material (for example, respiratory secretions) from a person who has SARS. Potential ways in which SARS can be spread include touching the skin of other people or objects that are contaminated with infectious droplets followed by touching of eye(s), nose, or mouth. This can happen when someone who is sick with SARS coughs or sneezes droplets onto themselves, other people, or nearby surfaces. It also is possible that SARS can be spread more broadly through the air or by other ways that are currently not known.
Scientists at the Centers for Disease Control and Prevention (CDC) and other laboratories around the world have detected a previously unrecognized coronavirus in patients with SARS. The evidence for a coronavirus was based on genetic fingerprint and electron microscopic ultrastructural studies and was widely reported in the popular press. Viologists at the CDC, WHO and numerous academic laboratories all reported that a coronavirus is the leading hypothesis for the cause of SARS.
The CDC recently reported sequencing the genome for SARS-CoV (Urbani strain), a strain of a novel human coronavirus believed to be responsible for SARS. The sequence data confirm that the SARS virus is a previously unrecognized coronavirus. The virus was cultured from cells taken from a throat culture taken from a SARS patients and grown in Vero cells (African green monkey kidney cells) in order to reproduce the ribonucleic acid (RNA) of the disease-causing coronavirus. The new sequence has 29,727 nucleotides, which places it well within the typical RNA boundaries for coronaviruses. Members of this viral family tend to have between 29,000 and 31,000 nucleotides. See Lai et al., Adv. Virus Res. 48:1, (1997). The genome organization of the SARS virus also is similar to that of other coronaviruses.
The genome sequence of SARS-CoV (Urbani) is available from GenBank at the Web site for the National Center for Biotechnology Information, National Library of Medicine http://www.ncbi.nim.nih.gov/. The accession number for the sequence of SARS-CoV (Urbani strain) is ay278741. The present inventors have used these sequence data to identify molecular targets that can be exploited to design safe and effective novel antiviral therapies that can be used to treat SARS and to stem the tide of the growing epidemic.